The pharmacological mechanism and molecular details of Platycodon grandiflorum in the treatment of novel coronavirus Pneumonia(COVID-19)

Background:Novel coronavirus pneumonia(COVID-19)has developed as a pandemic of global concern.There is an urgent need to develop effective and safe therapies.Platycodon grandiflorum(PG),one of the most famous traditional Chinese herbs,may be satisfied.In this study,we explored the pharmacological mechanism of PG in the treatment of COVID-19.Method:The active compounds and potential targets were acquired from public databases.The protein-protein interaction,the Gene Ontology,and the Kyoto Encyclopedia of Genes and Genomes were determined through bioinformatics analysis.Molecular docking and molecular dynamics were performed to further verify the findings.Result:A total of 38 bioactive ingredients and 276 gene targets of PG were identified.There were 78 intersected targets of PG and COVID-19.The network analysis revealed that luteolin,Platycogenic acid A,Platycogenic acid C,Polygalacic acid,and acacetin may be candidate agents.The AKT1,VEGFA,TP53,MAPK3,TNF,IL6,CASP3,EGFR,STAT3,and CCND1 were the important potential drug targets.Gene Ontology terms are involved in biological processes,which are mainly concentrated in inorganic substances and apoptosis,etc.The Kyoto Encyclopedia of Genes and Genomes pathway was involved in several aspects,such as Virus infection and immune regulation-related pathways.Molecular docking results showed that compounds of PG are closely bound to related targets.Molecular dynamics further found that Robin,Flavplatycoside,and dimethyl 3-O-β-D-glucopyranosylplatycogenate A can maintain good stability and flexibility in the composite system.Conclusion:PG has multicomponent,multitarget,and multichannel characteristics,which can provide an important theoretical basis to treat patients with COVID-19.

Application of zebrafish in the study of the gut microbiome

Zebrafish(D anio rerio)have attracted much attention over the past decade as a reliable model for gut microbiome research.Owing to their low cost,strong genetic and development coherence,efficient preparation of germ-f ree(GF)larvae,availability in high-t hroughput chemical screening,and fitness for intravital imaging in vivo,zebrafish have been extensively used to investigate microbiome-h ost interactions and evaluate the toxicity of environmental pollutants.In this review,the advantages and disadvantages of zebrafish for studying the role of the gut microbiome compared with warm-b looded animal models are first summarized.Then,the roles of zebrafish gut microbiome on host development,metabolic pathways,gut-b rain axis,and immune disorders and responses are addressed.Furthermore,their applications for the toxicological assessment of aquatic environmental pollutants and exploration of the molecular mechanism of pathogen infections are reviewed.We highlight the great potential of the zebrafish model for developing probiotics for xenobiotic detoxification,resistance against bacterial infection,and disease prevention and cure.Overall,the zebrafish model promises a brighter future for gut microbiome research.

Effects of long-term exposure to TDCPP in zebrafish( Danio rerio )–Alternations of hormone balance and gene transcriptions along hypothalamus-pituitary axes

Background : TDCPP is one of the major chemical of organophosphate flame retardants(OPFRs) that has been detected ubiquitously in both the environment and biota. Previously we observed that it influenced the concentrations of sex and thyroid hormones in a sex-dependent pattern, leading to reproductive impairments after short-term exposure in zebrafish. Here we investigate the consequences of longerterm exposure to TDCPP on the hypothalamic-pituitary-gonad(HPG), hypothalamicpituitary-i nterrenal(HPI), and hypothalamic-pituitary-thyroid(HPT) axes of zebrafish( Danio rerio).Methods : A 120-day exposure test to 0.005, 0.05 and 0.5 mg/L TDCPP was initiated with fertilized eggs. Sex steroid hormones in the treated fishes were measured and transcriptional changes were analyzed.Results : In female fish, exposure to TDCPP resulted in increases in plasma cortisol,follicle stimulating hormone(FSH), luteinizing hormone(LH), 17β-estradiol(E2), cortisol, thyroxine(T4), and triiodothyronine(T3). Transcription of most target genes along HPG, HPI and HPT axes were increased by the exposure. While in male fish the exposure led to decreases in cortisol, FSH, LH, T4, T3, testosterone(T), and 11-ketotestosterone(11-KT). Transcription of genes along HPG, HPI and HPT axes,especially steroidogenic genes, were inhibited in male zebrafish. While, E2/T or E2/11-KT ratio was increased in both female and females. The sex-dependent changes in hormones might be due to differential responses to TDCPP induced stresses. An increase in cortisol level coincided with increases in E2 and THs in female fish, while in males decreases in cortisol as well as T, 11-KT and THs were observed. Long-term exposure to TDCPP at very low(μg/L) concentrations could disrupt hormone balances in a sex dependent way.Conclusion : This study revealed that TDCPP could affect endocrine axes – HPG, HPI and HPT – in zebrafish, and impair zebrafish development.

Geographical Traceability of Clinacanthus nutans with Near-Infrared Pectroscopy and Chemometrics

In this study, a seed origin discrimination model for Clinacanthus nutans was developed. First, 81 C. nutans samples from three seed origin locations were collected, and their Near-Infrared (NIR) spectra were obtained. Next, Principal Component Analysis (PCA) was performed on the NIR spectra of the 81 C. nutans samples. Then, MSC (multiplicative scatter correction), SNV (standard normal variate), first derivative, and second derivative pre-treatments of the C. nutans spectra were performed and combined with the Support Vector Machine (SVM) algorithm for modelling and analysis. Among these methods, first-order derivative pre-treatment achieved the best SVM model effectiveness, with a training set accuracy of 93.44% (57/61) and a test set accuracy of 85.00% (17/20). In order to further improve the discrimination accuracy of the model, three optimization algorithms Grid Search (GS), Genetic Algorithm (GA), and Particle Swarm Optimization (PSO) were employed to identify the best c and g parameters for the SVM model. The results demonstrated that the PSO optimization algorithm yielded the best parameters of c = 0.8343, g = 57.8741, with corresponding model training set the accuracy of 96.36% (60/61) and test set the accuracy of 95.00% (20/21). Therefore, developing a seed origin classification model for C. nutans based on NIR spectroscopy combined with chemometrics is feasible and has the advantages of being simple, rapid, and green.

Astragalus Polysaccharide Enhances Voriconazole Metabolism under Inflammatory Conditions through the Gut Microbiota

Background and Aims:Voriconazole(VRC),a widely used antifungal drug,often causes hepatotoxicity,which presents a significant clinical challenge.Previous studies demonstrated that Astragalus polysaccharide(APS)can regulate VRC metabolism,thereby potentially mitigating its hepatotoxic effects.In this study,we aimed to explore the mechanism by which APS regulates VRC metabolism.Methods:First,we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale.Second,we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism.Various in vitro and in vivo assays,including cytokine profiling,immunohistochemistry,quantitative polymerase chain reaction,metabolite analysis,and drug concentration measurements,were performed using a lipopolysaccharideinduced rat inflammation model.Finally,experiments such as intestinal biodiversity analysis,intestinal clearance assessments,and Bifidobacterium bifidum replenishment were performed to examine the ability of B.bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut–liver axis.Results:The results indicated that APS does not have a direct effect on hepatocytes.However,the assessment of gut microbiota function revealed that APS significantly increases the abundance of B.bifidum,which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism.The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-B signaling pathway.Conclusions:The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage,highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

New insights into molecules and pathways of cancer metabolism and therapeutic implications

Cancer cells are abnormal cells that can reproduce and regenerate rapidly.They are characterized by unlimited proliferation,transformation and migration,and can destroy normal cells.To meet the needs for cell proliferation and migration,tumor cells acquire molecular materials and energy through unusual metabolic pathways as their metabolism is more vigorous than that of normal cells.Multiple carcinogenic signaling pathways eventually converge to regulate three major metabolic pathways in tumor cells,including glucose,lipid,and amino acid metabolism.The distinct metabolic signatures of cancer cells reflect that metabolic changes are indispensable for the genesis and development of tumor cells.In this review,we report the unique metabolic alterations in tumor cells which occur through various signaling axes,and present various modalities available for cancer diagnosis and clinical therapy.We further provide suggestions for the development of anti-tumor therapeutic drugs.

Self-enhanced photothermal-chemodynamic antibacterial agents for synergistic anti-infective therapy

Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion property.However,they still suffer from shortage of Cu(Ⅰ)supply in the long-term and comparatively low inherent photothermal conversion efficiency.Herein,we constructed a self-enhanced synergistic PTT/CDT nanoplatform(Cu_(1.94)S@MPN)by coating Cu_(1.94)S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks(MPN).Activated by the acidic bacterial infection microenvironment,Cu_(1.94)S@MPN could be decomposed to continuously release Cu(Ⅱ),Fe(Ⅲ)ions and tannic acid.As the result of tannic acid-involved Cu and Fe redox cycling,Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like reactions.More importantly,experimental results demonstrated that Cu_(1.94)S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in vivo.Overall,this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.

Autophagy-associated long non-coding RNA signature for lung adenocarcinoma

Background:Autophagy-associated long non-coding RNAs(aalncRNAs)take an important position in the tumorigeness of lung cancer,but current researches have not systematically investigated autophagy-associated lncRNAs in lung adenocarcinoma(LUAD).Methods:In this research,RNA-sequences of LUAD patients were downloaded from the TCGA and autophagy-associated genes were obtained from the GSEA website.The Pearson's test was conducted to find the correlation between autophagy-associated lncRNAs and autophagy-associated genes.AalncRNAs with prognostic significance were identified by using Cox and LASSO regression analysis in R,gradually.Risk score model was built to estimate prognosis-associated lncRNAs.Results:A risk score model was established according to the expressions of 7 aalncRNAs(RP11-102K13.5,RP11-1029J19.4,LINC00942,KLHL7-AS1,AC092198.1,C20orf197,LINC01116),and low-risk group was found to have a better prognosis(P<0.001).Next,single gene expression survival analysis show that 4 out of these lncRNAs were significantly associated with the survival of patients.In addition,the AUC value of model reached 0.724,demonstrating the good predictive ability of the model.Conclusion:These aalncRNAs in LUAD might possibly offered biological markers for the diagnosis and therapy of lung adenocarcinoma.